1-111477409-C-G

Variant names:

• chr1-111477409-C-G
• rs868833678
• NM_001300834.2:c.183C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001300834.2(C1orf162):​c.183C>G​(p.Ile61Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: C1orf162 NM_001300834.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.746
• Publications: 0 publications found

Genes affected

C1orf162 (HGNC:28344): (chromosome 1 open reading frame 162) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27847844).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300834.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf162	NM_001300834.2	MANE Select	c.183C>G	p.Ile61Met	missense	Exon 4 of 6	NP_001287763.1	Q8NEQ5-2
	C1orf162	NM_174896.4		c.183C>G	p.Ile61Met	missense	Exon 4 of 6	NP_777556.1	Q8NEQ5-1
	C1orf162	NM_001300835.2		c.116-242C>G		intron	N/A	NP_001287764.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf162	ENST00000369718.4	TSL:2 MANE Select	c.183C>G	p.Ile61Met	missense	Exon 4 of 6	ENSP00000358732.3	Q8NEQ5-2
	C1orf162	ENST00000343534.9	TSL:1	c.183C>G	p.Ile61Met	missense	Exon 4 of 6	ENSP00000344218.5	Q8NEQ5-1
	C1orf162	ENST00000868017.1		c.183C>G	p.Ile61Met	missense	Exon 4 of 6	ENSP00000538076.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251428 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460932 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726848

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.000157 AC: 7 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111146

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.056
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.75
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.28		Gain of catalytic residue at I61 (P = 0.0154)
MVP		0.14
MPC		0.74
ClinPred		0.83	D
GERP RS		3.2
Varity_R		0.34
gMVP		0.13
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs868833678; hg19: chr1-112020031;